The three major projects described in this proposal are designed to provide a better understanding of the physiological mechanisms by which hypertension develops; it is only when these mechanisms are fully understood that a rational and physiological approach to treatment can be devised and effective consideration given to prevention of the disease. There are three main thrusts: (1) An increase in cardiac output has been shown to precede and accompany onset of renal hypertension. This may be a vital key in understanding etiology and the mechanism involved will be investigated from the point of view of change in fluid spaces, the role of capacitance vessels and change in myocardial function. (2) Angiotensin has a central action on vasomotor centers to raise arterial pressure; it is important to determine if this action contributes to the neurogenic component of renal hypertension and to establish its nature and the specific areas affected. (3) Renin has been shown to occur in peripheral blood vessels and we have demonstrated that it can be released under certain circumstances by sympathetic stimulation. Clarification of the function of these peripheral stores could provide an explanation for low plasma renin levels in renal hypertension and possibly explain why antirenin lowers arterial pressure in hypertensive animals while immunization against angiotensin does not.